Many diagnostic methods rely on the ability to distinguish one set of organisms from another (e.g., pathogenic bacteria from non-pathogenic bacteria). Some such methods are based on polymerase chain reaction (PCR) assays that distinguish a particular genome or set of genomes from other genomes. Current methods for finding PCR primers specific to certain species or strains typically involve identifying genomic signatures, regions in which every k-mer in the sequence is unique to a target set of genomes but not found in genomes of other organisms.